Selective Breeding, Quantitative Trait Locus Analysis, and Gene Arrays Identify Candidate Genes for Complex Drug-Related Behaviors
| Autor: | Boris Tabakoff, Sanjiv V. Bhave, Paula L. Hoffman |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Male
Candidate gene Quantitative Trait Loci Mice Inbred Strains Breeding Quantitative trait locus Biology Polymerase Chain Reaction Mice CCAAT-Enhancer-Binding Protein-alpha Animals Genetic Predisposition to Disease Ephrin B3 Promoter Regions Genetic Postural Balance Gene Oligonucleotide Array Sequence Analysis Zinc finger Genetics Binding Sites Behavior Animal Ethanol Gene Expression Profiling General Neuroscience Brain Chromosome Mapping Drug Tolerance Phenotype Alcohol-Induced Disorders Ataxia Signal transduction DNA microarray Cellular/Molecular Transcription Factors |
| Zdroj: | The Journal of Neuroscience. 23:4491-4498 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.23-11-04491.2003 |
| Popis: | Acute functional tolerance to ethanol develops during a single exposure to ethanol; it has been suggested to be a predisposing factor for the development of ethanol dependence. Genetic determinants of acute functional tolerance, as well as of ethanol dependence, have been clearly demonstrated. We describe a novel approach that uses a combination of selective breeding (to segregate genes contributing to the phenotype of interest, i.e., acute functional tolerance to the incoordinating effect of ethanol), quantitative trait locus analysis (to define chromosomal regions associated with acute functional tolerance), and DNA microarray technology (to identify differentially expressed genes in the brains of the selected lines of mice) to identify candidate genes for the complex phenotype of ethanol tolerance. The results indicate the importance of a signal transduction cascade that involves the glutamate receptor δ2 protein, the Ephrin B3 ligand, and the NMDA receptor, as well as a transcriptional regulatory protein that may be induced by activation of the NMDA receptor (zinc finger protein 179) and a protein that can modulate downstream responses to NMDA receptor activation (peroxiredoxin), in mediating acute tolerance to the incoordinating effect of ethanol. |
| Databáze: | OpenAIRE |
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